AU607941B2 - Active compounds for preventing tumor metastases - Google Patents
Active compounds for preventing tumor metastases Download PDFInfo
- Publication number
- AU607941B2 AU607941B2 AU79996/87A AU7999687A AU607941B2 AU 607941 B2 AU607941 B2 AU 607941B2 AU 79996/87 A AU79996/87 A AU 79996/87A AU 7999687 A AU7999687 A AU 7999687A AU 607941 B2 AU607941 B2 AU 607941B2
- Authority
- AU
- Australia
- Prior art keywords
- acid
- tumor metastases
- active compounds
- preventing tumor
- antipodes
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/275—Nitriles; Isonitriles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
The use of (+)-verapamil, (+)-gallopamil, (+)-devapamil and/or (+)-emopamil for preventing tumour metastases is described.
Description
Form COMMONWEALTH OF AUSTRALIA PATENTS ACT 1952-69 COMPLETE SPECIRiCATION (OR IGINAL) Class Application Number: I t. Class Lodged: 607941t Complete Spe-.f ication Lodged: Accepted: Published: 'Priof ity' 1 00 Related Art.: This document contains the amnendm-ents made under Section 49 and is correcE for printi ng, ,,Name of Applicant.
Address of Applicant: 0 Actual Inventor: At~dress for Service: BASF AKTIENGESELLSCHAFT D-6700 Ludwigshafen, Federal Republic of Germany WERNER SEITZ, LOTHAR DAUM, FRANZ EMLING and GERHARD
KEILHAUEP
EDWD. WATERS SONS, 50 QUE EN STREET, MELBOURNE, AUSTRALIA, 3000.
Comgijlote Specification for the Invention entitled: ACTIVE COMPOUNDS FOR PREVENTING TUMJR METASTASES The following statement is a full description of this Invention, includIng the uest method of performing it known to u 1 O.Z. 0050/38747 Active compounds for preventing tumor metastases German Patent 1,154,810 describes phenylacetonitriles which are substituted by basic groups. From this class of compounds, verapamil and gatlopamil have proven useful in the therapy of coronary heart disease and of high blood pressure, owing to their caLcium-antagonistic action. Both compounds are used in the racemic form in therapy. German Laid-Open Application DOS 2,059,923 describes.the levorotatory antipodes of verapamil and gallopamil. Both compounds have a substantially superior coronary efficacy compared with the racemate. German Patent 2,059,985 discloses the dextrorotatory antipodes of verapamil and gallopai'i! The separation between antiarrhythmic action and negative irotropic action is sub- 15 stantially more advantageous in the dextrorotatory anti- 0 0 0 00oo podes.
000 °o 0° European Laid-Open Application 147,707 describes 00 0 O"ao the antipodes of emcpamil and their use for the protec- 0 0 tive treatment of hypoxic tissue damage, Both enantio- 00 0 o 20 mers have a dose-dependent protective action. The effec- .0o" tive dose of the tevorotatory antipodes is lower than that of the dextrorotatory antipodes by a factor of from 8 to 0 000 Soo The substantial superiority of the Levorotatory B 0O antipodes of verapamit, gallopamit and devapamil with regard to cardiac action is also described by H. Nawrath and ae M. Raschack (Cell. Calcium 5 (1984), 316). The calcium- 0 t antagonistic action of the Levorotatory antipodes is superior to that of the dextrorotatory antipodes by a factor of 0 0 30 up to 200. In the negative inotropic action, the difference has been found to correspond to a factor of up to Furthermore, European Laid-Open Application 159,678 and the publication by T. Tsuruo et al. (Cancer Chemother. Pharmacol. 14 (1985), 30) describe the use of racemic verapamil for the treatment of tumor metastases. The therapeutic 4oses administered there are restricted and cannot be employed since the intrinsic cardiac 2 0.Z. 0050/38747 action of verapamiL prevents such high doses being uised in pract ice in human medic ine.
Surprisingly, we have found that the two enantiomeric forms of verapaniiL, gaLLopaiaiL, devapamit and emoparniL do not differ in the inhibition of spontaneous and experimental tumor metastases. Since the cardiac action of the racemates is predominantLy due to the tevoratatory antipodes, the use of the dlextrorotatory enantiomers offers the possibility of administering sufficiently high doses whiLe at the same time minimizing the intrinsic cardiac action. This constitutes a substantiaL improvement of the therapeutic index.
The present invention reLates to the use of verapamil, (+)-gaLtopamiL, (+)-devtapamiL and/or 15 emopamiL for the prevention of tumor metastases, and the o 00 0000 use of these substances for the preparation of drugs for 00o the prevention of tumor metastases.
Q 0 0Verapamil is 5-E (3,4-dimethoxyphenethyl )-methyL- 0 0 0 0 0 Oq 2 gaLLopamiL is 5-[,(3,4-dime thoxyphenethyL )-methyL amino 3- 000 2-isopropyL-2-(3,4,5-trimethoxyphenyL )-vaLeronitriLe, devapamiL is 5-C (3-me thoxyphenethyL )-me thyt amino 3-2-iso- 00 propyL-2-(3,4-dimethoxyphenyt )-valeron itr iLe and 0 Q00 emopamil is 5-1(phenethyl)-methytamino3-2-isopropyL-2- 4 025 phenyLvateronitrie.
0000 000I b The abovementioned sub tqce~s an, if d sred, bin the form of their sal ts wit acids.
.0.000 0Preferred physiologjicatLy tolerated acids are hydrochtoric 000 0 acid, sulfuric acid, phosphoric acid, acetic acid, cite 0 0:0 a 30 ric acid, inatonic acid, saLicyLic acid, rnaleic acid, 0, 00 fumaric acid, succinic acid, ascorbic acid, malc acid, methanesuLfonic acid, Lactic acid, gLuconic acid, gtucuron ic ac idc, am idosu Lf on ic ac id, benzo ic ac id and tartaric acid.
The dosage of the stated substances as antimetastatic agents differs depending on the type of cancer and on the stage of the L~sease. As a ruLe., the dlaiLy 1 3 O.Z. 0050/38747 dose for aduLts is from 300 to 1,000 mg per day for oral administration, from 200 to 300 mg per day for intravenous administration and from 200 to 500 mg per day for intr aperitoneal administration.
The substances can be in the form of tablets, capsuLes or coated tablets for oral administration or in the form of an injection solution for parenteral (intravenous, intraperitoneal or intramuscular) administration. Solutions may also be infused. The administration forms are prepared in a known ,anner by conventional methods.
The substances can also be administered to patients who have already been subjected, or are being subjected, to other tumor therapies, for example chemotherapy, endocrinotherapy, 'imunotherapy, radiation or surgery.
0 00 EXAMPLE 00oo 0o oo Oblong tablets having the following composition 00 0 ono are prepared in the conventional manner: 00 0 ooo 500 mg of (+)-verapamil, o 0 20 120 mg of Lactose, 0 0 S°ooe 60 mg of cellulose, 3 mg of magnesium stearate, 50 mg of corn starch and O O o 15 mg of poLyvinylpyrrolidone.
000ooo O 0 0000 0 4 000 00 0
Claims (1)
1. A method of treatment of tumour metastases comprising administering to a patient suffering therefrom, a pharmaceutically effective amount of -gallopamil, -devapamil, -veraparnil or -emopamil. DATED this 13th day of December, 1990 C ~BASF AKTIEN4GESELLSCHAFT WATERMARK~ PATENT &TRADEMARK~ ATTORNWEYS THE ATRIUM 00 0 290 BUIRWOOD ROAD HAWTHORN, VICTORIA 3122 AUSTRALIA 0000 0000 o 00C 00 0 00 LCG/KJS:JJC 0 0 0 00 (6/16)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3635931 | 1986-10-22 | ||
| DE19863635931 DE3635931A1 (en) | 1986-10-22 | 1986-10-22 | ACTIVE SUBSTANCES FOR PREVENTING TUMOR METASAS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU7999687A AU7999687A (en) | 1988-04-28 |
| AU607941B2 true AU607941B2 (en) | 1991-03-21 |
Family
ID=6312240
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU79996/87A Ceased AU607941B2 (en) | 1986-10-22 | 1987-10-21 | Active compounds for preventing tumor metastases |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0270782B1 (en) |
| JP (1) | JPS63264414A (en) |
| AT (1) | ATE79255T1 (en) |
| AU (1) | AU607941B2 (en) |
| DE (2) | DE3635931A1 (en) |
| ES (1) | ES2051721T3 (en) |
| ZA (1) | ZA877900B (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3635930A1 (en) * | 1986-10-22 | 1988-04-28 | Basf Ag | ACTIVE SUBSTANCES FOR TUMOR TREATMENT |
| DE3826796A1 (en) * | 1988-08-06 | 1990-02-08 | Basf Ag | SUBSTITUTED PHENYL ACETONITRILE FOR USE AS A RESISTANCE BREAKER |
| DE3928287A1 (en) * | 1989-08-26 | 1991-02-28 | Knoll Ag | USE OF THE (+) - ENANTIOMER OF ANIPAMIL |
| AU3205497A (en) * | 1996-05-23 | 1997-12-09 | G.D. Searle & Co. | Pharmaceutical compositions containing non-racemic verapamil and process for optimizing the pharmaceutical activity of r- and s-verapamil |
| WO2002043730A1 (en) * | 2000-11-29 | 2002-06-06 | Epidauros Biotechnologie Ag | Use of mdr-1 inducers for treating or preventing diseases |
| US20030092765A1 (en) * | 2001-11-15 | 2003-05-15 | John Kelly | Treatment of abnormal increases in gastrointestinal motility with (R)-verapamil |
| US10100313B2 (en) * | 2014-02-10 | 2018-10-16 | Institut Curie | Use of Mcoln-1 modulators to regulate cell migration |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU7999787A (en) * | 1986-10-22 | 1988-04-28 | Basf Aktiengesellschaft | Active compounds for use in the treatment of tumors |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2059985C3 (en) * | 1970-12-05 | 1979-10-04 | Knoll Ag, 6700 Ludwigshafen | Right-handed, basic substituted phenylacetonitriles, processes for their preparation and pharmaceuticals containing these compounds |
| US4690935A (en) * | 1983-03-31 | 1987-09-01 | Wayne State University | Inhibition of tumor growth and metastasis with calcium channel blocker compounds |
| JPH0753665B2 (en) * | 1984-04-20 | 1995-06-07 | 財団法人癌研究会 | Anti-metastatic agent |
-
1986
- 1986-10-22 DE DE19863635931 patent/DE3635931A1/en not_active Withdrawn
-
1987
- 1987-10-20 JP JP62262940A patent/JPS63264414A/en active Pending
- 1987-10-21 ZA ZA877900A patent/ZA877900B/en unknown
- 1987-10-21 ES ES87115378T patent/ES2051721T3/en not_active Expired - Lifetime
- 1987-10-21 EP EP87115378A patent/EP0270782B1/en not_active Expired - Lifetime
- 1987-10-21 AT AT87115378T patent/ATE79255T1/en not_active IP Right Cessation
- 1987-10-21 AU AU79996/87A patent/AU607941B2/en not_active Ceased
- 1987-10-21 DE DE8787115378T patent/DE3781116D1/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU7999787A (en) * | 1986-10-22 | 1988-04-28 | Basf Aktiengesellschaft | Active compounds for use in the treatment of tumors |
Also Published As
| Publication number | Publication date |
|---|---|
| DE3781116D1 (en) | 1992-09-17 |
| ZA877900B (en) | 1989-06-28 |
| JPS63264414A (en) | 1988-11-01 |
| ATE79255T1 (en) | 1992-08-15 |
| DE3635931A1 (en) | 1988-04-28 |
| EP0270782B1 (en) | 1992-08-12 |
| EP0270782A3 (en) | 1990-01-03 |
| AU7999687A (en) | 1988-04-28 |
| ES2051721T3 (en) | 1994-07-01 |
| EP0270782A2 (en) | 1988-06-15 |
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